Safety of Drugs Used in Hospitalized Infants

Examining the safety of more than 10 medications in hospitalized infants using a large database with information from electronic health records.


Only 25% of approved drugs marketed in the United States have sufficient pediatric data to support product labeling by the FDA for dosing, safety, or efficacy in children. As a result, the majority of drugs administered to children are used off-label. Clinical trials to evaluate the safety of these drugs are lacking across pediatric age groups, due, in part, to concerns about exposing pediatric patients to the risks of prospective drug studies.

Retrospective observational studies carry minimal risk for participants. The use of a large database usually provides samples sizes large enough to make inferences about the population in question. In this PTN study, we will use the Pediatrix Medical Group database—a database prospectively created from electronic health records of infants admitted to more than 300 neonatal intensive care units (NICUs) in the United States. It is one of the largest repositories of data in neonatal medicine; the database includes approximately 22% of NICU patients nationally and over 90,000 NICU admissions annually.

Using retrospective data analysis techniques, we will estimate the incidence of adverse events for hospitalized infants exposed to drugs of interest, including proton pump inhibitors, octreotide, and 8 additional therapeutics. These results will be compared against those from an FDA pediatric pilot study comprising a network of 6 hospitals seeking to better understand both indications for off-label use and incidences of adverse events. The comparison of frequency of adverse events from the Pediatrix database and the FDA pediatric pilot study will facilitate understanding of the most appropriate information system for studying drug use and adverse events in infants.


Cefepime and Ceftazidime Safety in Hospitalized Infants.
Arnold CJ, Ericson JE, Cho N, Tian J, Wilson S, Chu VH, Hornik CP, Clark RH, Benjamin Jr. DK, and Smith PB, on behalf of the Best Pharmaceuticals for Children Act – Pediatric Trials Network Administrative Core Committee.
Pediatric Infectious Disease Journal • September 2015, volume 34, issue 9, pages 964-968.
PMCID: PMC4573537 [Free access available on 9/1/2016]

Safety of octreotide in hospitalized infants.
Testoni D, Hornik CP, Neely ML, Yang Q, McMahon AW, Clark RH, Smith PB; Best Pharmaceuticals for Children Act — Pediatric Trials Network Administrative Core Committee.
Early Human Development • July 2015, volume 91, issue 7, pages 387-392.
PMCID: PMC4450124 [Free access available on 7/1/2016]

Safety of milrinone use in neonatal intensive care units.
Samiee-Zafarghandy S, Raman SR, van den Anker JN, McHutchison K, Hornik CP, Clark RH, Brian Smith P; Best Pharmaceuticals for Children Act—Pediatric Trials Network Administrative Core Committee.
Early Human Development • January 2015, volume 91, issue 1, pages 31-35.
PMCID: PMC4302030 [Free PMC article]

Medication use in the neonatal intensive care unit.
Hsieh EM, Hornik CP, Clark RH, Laughon MM, Benjamin DK Jr, Smith PB; Best Pharmaceuticals for Children Act—Pediatric Trials Network.
American Journal of Perinatology • October 2014, volume 31, issue 9, pages 811-821.
PMCID: PMC4061287 [Free PMC article]

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Published; clinical study report submitted to FDA

Principal Investigators:
Daniel K. Benjamin, MD, PhD, MPH and P. Brian Smith, MD, MPH, MHS
Duke Health, Durham, NC


  • The Pharmacometrics Core of the PTN August 21, 2013 Edmund Capparelli, PharmD, chair of the Pharmacometrics Core of the Pediatric Trials Network, explains the role of pharmacometrics in improving medical treatments for infants and children.
  • The Clinical Pharmacology Core of the PTN May 7, 2013 Greg Kearns, chair of the PTN Clinical Pharmacology Core, explains how clinical pharmacology helps to make medicines safer for children.